Transcriptomic HIV-1 reservoir profiling reveals a role for mitochondrial functionality in HIV-1 latency.
Identifying cellular and molecular mechanisms maintaining HIV-1 latency in the viral reservoir is crucial for devising effective cure strategies. Here we developed an innovative flow cytometry-fluorescent in situ hybridization (flow-FISH) approach for direct ex vivo reservoir detection without the n...
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| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2025-01-01
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| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1012822 |
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| author | Shirley Man Jade Jansen Stefanie Kroeze Teunis B H Geijtenbeek Neeltje A Kootstra |
| author_facet | Shirley Man Jade Jansen Stefanie Kroeze Teunis B H Geijtenbeek Neeltje A Kootstra |
| author_sort | Shirley Man |
| collection | DOAJ |
| description | Identifying cellular and molecular mechanisms maintaining HIV-1 latency in the viral reservoir is crucial for devising effective cure strategies. Here we developed an innovative flow cytometry-fluorescent in situ hybridization (flow-FISH) approach for direct ex vivo reservoir detection without the need for reactivation using a combination of probes detecting abortive and elongated HIV-1 transcripts. Our flow-FISH assay distinguished between HIV-1-infected CD4+ T cells expressing abortive or elongated HIV-1 transcripts in PBMC from untreated and ART-treated PWH from the Amsterdam Cohort Studies. This flow-FISH method was employed to isolate CD4+ T cells expressing abortive or elongated HIV-1 transcripts from five ART-naïve PWH for transcriptomic analysis by 3' RNA sequencing. Supervised cluster analysis identified several differentially expressed mitochondrial genes in infected CD4+ T cells with abortive HIV-1 transcripts compared to cells containing elongated HIV-1 transcripts. Notably, enhancing mitochondrial function induced HIV-1 transcription in PBMC from PWH. Our data strongly suggests that cellular metabolism is involved in maintaining HIV-1 latency and show that improving mitochondrial functions induces HIV-1 transcriptional activity in PWH. These findings underline the relevance of metabolic regulation in HIV-1 infection, and support the development of strategies modulating immunometabolism to target viral latency. |
| format | Article |
| id | doaj-art-e5d110477f4d4961a86d8e7d85abb1b0 |
| institution | Kabale University |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-e5d110477f4d4961a86d8e7d85abb1b02025-01-17T05:31:03ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742025-01-01211e101282210.1371/journal.ppat.1012822Transcriptomic HIV-1 reservoir profiling reveals a role for mitochondrial functionality in HIV-1 latency.Shirley ManJade JansenStefanie KroezeTeunis B H GeijtenbeekNeeltje A KootstraIdentifying cellular and molecular mechanisms maintaining HIV-1 latency in the viral reservoir is crucial for devising effective cure strategies. Here we developed an innovative flow cytometry-fluorescent in situ hybridization (flow-FISH) approach for direct ex vivo reservoir detection without the need for reactivation using a combination of probes detecting abortive and elongated HIV-1 transcripts. Our flow-FISH assay distinguished between HIV-1-infected CD4+ T cells expressing abortive or elongated HIV-1 transcripts in PBMC from untreated and ART-treated PWH from the Amsterdam Cohort Studies. This flow-FISH method was employed to isolate CD4+ T cells expressing abortive or elongated HIV-1 transcripts from five ART-naïve PWH for transcriptomic analysis by 3' RNA sequencing. Supervised cluster analysis identified several differentially expressed mitochondrial genes in infected CD4+ T cells with abortive HIV-1 transcripts compared to cells containing elongated HIV-1 transcripts. Notably, enhancing mitochondrial function induced HIV-1 transcription in PBMC from PWH. Our data strongly suggests that cellular metabolism is involved in maintaining HIV-1 latency and show that improving mitochondrial functions induces HIV-1 transcriptional activity in PWH. These findings underline the relevance of metabolic regulation in HIV-1 infection, and support the development of strategies modulating immunometabolism to target viral latency.https://doi.org/10.1371/journal.ppat.1012822 |
| spellingShingle | Shirley Man Jade Jansen Stefanie Kroeze Teunis B H Geijtenbeek Neeltje A Kootstra Transcriptomic HIV-1 reservoir profiling reveals a role for mitochondrial functionality in HIV-1 latency. PLoS Pathogens |
| title | Transcriptomic HIV-1 reservoir profiling reveals a role for mitochondrial functionality in HIV-1 latency. |
| title_full | Transcriptomic HIV-1 reservoir profiling reveals a role for mitochondrial functionality in HIV-1 latency. |
| title_fullStr | Transcriptomic HIV-1 reservoir profiling reveals a role for mitochondrial functionality in HIV-1 latency. |
| title_full_unstemmed | Transcriptomic HIV-1 reservoir profiling reveals a role for mitochondrial functionality in HIV-1 latency. |
| title_short | Transcriptomic HIV-1 reservoir profiling reveals a role for mitochondrial functionality in HIV-1 latency. |
| title_sort | transcriptomic hiv 1 reservoir profiling reveals a role for mitochondrial functionality in hiv 1 latency |
| url | https://doi.org/10.1371/journal.ppat.1012822 |
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